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Apolipoprotein E (apo E) is one of the apolipoprotein components in very low density lipoproteins (VLDL) and high density lipoproteins (HDL). Apo E binds to low density lipoprotein (LDL) receptors and apo E-specific remnant receptors, and regulates remnant lipoprotein metabolism through these receptors in the liver. In the general population, apo E shows genetic heterogeneity, with three alleles (epsilon 4, epsilon 3, and epsilon 4) which produce apo E isoproteins, apo E4, apo E3, and apo E2, respectively. Apo E2 is defective in its binding to lipoprotein receptors, resulting in the accumulation of lipoprotein remnants in the plasma. Type III hyperlipoproteinemia appears in a few percent of the individuals who are homozygous for apo E2 and the development of hyperlipoproteinemia requires the presence of other genetic or environmental factors. Even heterozygous individuals with apo E2 or apo E4 differ from those with only apo E3 in plasma lipoprotein metabolism. Subjects with an E3/2 phenotype had reduced LDL and increased VLDL levels, and those with an E4/3 phenotype had increased LDL levels in serum. In addition to these common apo E isoproteins, there are several unique mutants of apo E, which are associated with hyperlipoproteinemia and atherosclerosis.

Epidemiological studies have demonstrated that high density lipoprotein cholesterol (HDL-C) is inversely related to the incidence of coronary heart disease morbidity and mortality. In the present paper, we summarized the recently published data on HDL receptor, reverse cholesterol transport, and antiatherogenic effect of HDL particle. Several investigators have reported the apparent molecular weight of HDL binding protein using ligand blotting by radiolabeled HDL and immunoblotting by antibody against the purified binding protein. These results, however, were not consistent among the data reported from several laboratories. In 1992 a cDNA of HDL binding protein (HBP) was isolated from a human fibroblast and a human erythroleukemia cell cDNA library but it does not contain a classical hydrophobic membranes spanning domain. At present, it is reasonable to assume that HBP is different structurally and functionally from a classical plasma membrane receptor. We hope putative HDL receptor will be isolated, characterized and its cDNA will be cloned in the near future. It has been postulated that there are four functional steps in the pathway of reverse cholesterol transport. The main step is CETP-mediated transfer of cholesteryl esters from HDL to the VLDL/LDL fraction. Recent development of molecular biological techniques enable us to make a animal model over expressing apolipoprotein A-I or A-II, namely a transgenic mouse. These models indicated that apolipoprotein A-I has an antiatherogenic effect in vivo but apolipoprotein A-II does not.

Recent advances in lipoprotein metabolism were reviewed. The scavenger receptor for acetyl-LDL cloned by Kodama et al. was immunohistochemically demonstrated to exist in the human atherosclerotic lesions. LDL-receptor related protein (LRP) and VLDL receptor which would recognize apoE but not apoB have been recently cloned. Transgenic mice expressing high levels of apolipoproteins such as apoA-I and apoE or apolipoprotein deficient mice produced by gene targetting technique are providing important information on the function of apolipoproteins.